PROJECT DESCRIPTION One critical diagnostic criterion of an alcohol use disorder is the disproportionate time spent seeking and obtaining alcohol. A considerable body of preclinical data in animals now suggests that ventral striatal dopamine release is associated, not only with the response to reward cues, but also with reward seeking behaviors. This leaves a critical need to determine if and how human ventral striatal dopamine is related to alcohol-seeking behaviors. The objective of this application is to determine if human ventral striatal dopamine release is related to alcohol seeking behaviors. Our rationale for examining this phenomenon is that a key feature of alcohol use disorders involves disproportionate behavioral effort directed toward gaining access to alcohol. Our central hypothesis is that the cognitive and behavioral effort expended to gain access to alcohol is linked to human ventral striatal dopamine release. Using a task that requires goal-directed behaviors to gain access to ad lib alcohol, our specific aims are to conduct two experiments using dopaminergic positron emission tomography that will: Aim 1: Determine if instrumental efforts exerted to gain access to alcohol (alcohol seeking behaviors) are associated with human ventral striatal dopaminergic release. Hypothesis 1a: Alcohol seeking behaviors increase ventral striatal dopamine release. Hypothesis 1b: Alcohol craving during alcohol- seeking behaviors is positively correlated with ventral striatal dopamine release. Aim 2: Determine if alcohol cue exposure potentiates ventral striatal dopaminergic release during alcohol seeking behaviors. Hypothesis 2a: Exposure to the sensory cues of a preferred alcoholic drink will potentiate ventral striatal dopamine release during effortful alcohol seeking behaviors. Hypothesis 2b: Cue- potentiated alcohol craving during alcohol-seeking behaviors is positively correlated with ventral striatal dopamine release. Exploratory aim: Determine if ventral striatal dopamine release during alcohol seeking is associated with variables related to alcohol use and abuse. Here we explore the extent to which the magnitude of ventral striatal dopamine release during seeking behaviors is related to subjective reinforcement from alcohol, alcohol use patterns (self-reported, and observed during intravenous self-administration), alcohol-related problems, and trait impulsivity.